The outer coverings of the skeleton, which is also known as the periosteum, are arranged in concentric layers and act as a reservoir for tissue-specific bone progenitors. The cellular heterogeneity within this tissue depot is being increasingly recognized. Here, inducible PDGFRα reporter animals were found to mark a population of cells within the periosteum that act as a stem cell reservoir for periosteal appositional bone formation and fracture repair. During these processes, PDGFRα reporter⁺ progenitors give rise to Nestin⁺ periosteal cells before becoming osteoblasts and osteocytes. The diphtheria toxin-mediated ablation of PDGFRα reporter⁺ cells led to deficits in cortical bone formation during homeostasis and a diminutive hard callus during fracture repair. After ossicle transplantation, both mouse PDGFRα reporter⁺ periosteal cells and human Pdgfrα⁺ periosteal progenitors expand, ossify, and recruit marrow to a greater extent than their counterpart periosteal cells, whereas PDGFRα reporter⁻ periosteal cells exhibit a predisposition to chondrogenesis in vitro. Total RNA sequencing identified enrichment of the secreted factors Fermt3 and Ptpn6 within PDGFRα reporter⁺ periosteal cells, which partly underlie the osteoblastogenic features of this cell population.

骨骼的外部覆盖物，也称为骨膜，排列成同心层，充当组织特异性骨祖细胞的储存库。这个组织库内的细胞异质性越来越得到认可。在这里，发现可诱导的 PDGFRα 报告动物标记骨膜内的细胞群，这些细胞充当骨膜附着骨形成和骨折修复的干细胞库。在这些过程中，PDGFRα 报告基因⁺祖细胞在成为成骨细胞和骨细胞之前产生巢蛋白^{+骨膜细胞。}白喉毒素介导的 PDGFRα 报告基因的消融⁺细胞在体内平衡期间导致皮质骨形成缺陷，在骨折修复期间导致小的硬骨痂。小骨移植后，小鼠PDGFRα 报告基因⁺骨膜细胞和人 Pdgfrα ⁺骨膜祖细胞比其对应的骨膜细胞更大程度地扩张、骨化和募集骨髓，而 PDGFRα 报告基因^-骨膜细胞在体外表现出软骨形成的倾向。总 RNA 测序鉴定了 PDGFRα报告基因⁺骨膜细胞中分泌因子Fermt3和Ptpn6的富集，这部分是该细胞群的成骨细胞形成特征的基础。